Association of Polygenic Liability for Autism With Face-Sensitive Cortical Responses From Infancy.
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ABSTRACT:
SUBMITTER: Gui A
PROVIDER: S-EPMC8185629 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature
Publications
Association of Polygenic Liability for Autism With Face-Sensitive Cortical Responses From Infancy.
Gui Anna A Meaburn Emma L EL Tye Charlotte C Charman Tony T Johnson Mark H MH Jones Emily J H EJH
JAMA pediatrics 20210901 9
Similar Datasets
Project description:BackgroundFace detection, an ability to identify a visual stimulus as a face, is impaired in patients with schizophrenia. It is unclear whether impaired face processing in this psychiatric disorder results from face-specific domains or stems from more basic visual domains. In this study, we examined cortical face-sensitive N170 response in schizophrenia, taking into account deficient basic visual contrast processing.MethodsWe equalized visual contrast signals among patients (n=20) and controls (n=20) and between face and tree images, based on their individual perceptual capacities (determined using psychophysical methods). We measured N170, a putative temporal marker of face processing, during face detection and tree detection.ResultsIn controls, N170 amplitudes were significantly greater for faces than trees across all three visual contrast levels tested (perceptual threshold, two times perceptual threshold and 100%). In patients, however, N170 amplitudes did not differ between faces and trees, indicating diminished face selectivity (indexed by the differential responses to face vs. tree).ConclusionThese results indicate a lack of face-selectivity in temporal responses of brain machinery putatively responsible for face processing in schizophrenia. This neuroimaging finding suggests that face-specific processing is compromised in this psychiatric disorder.
| S-EPMC4707115 | biostudies-literature
Project description:The aim of this study was to examine specialized face processing in forty-eight 4.5- to 7.5-month-old infants by recording event-related potentials (ERPs) in response to faces and toys, and to determine the cortical sources of these signals using realistic, age-appropriate head models. All ERP components (i.e., N290, P400, Nc) showed greater amplitude during periods of attention than inattention. Amplitude was greater to faces than toys during attention at the N290, and greater to toys at the P400. Cortical source analysis revealed activity in occipital-temporal brain areas as the source of the N290, particularly the middle fusiform gyrus. The Nc and P400 were the result of activation in midline frontal and parietal, anterior temporal, and posterior temporal and occipital brain areas.
| S-EPMC5042801 | biostudies-literature
Project description:BackgroundThere are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity.MethodsWe tested the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: the Collaborative Genetic Study of Nicotine Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317 control subjects). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to the 1000 Genomes reference panel.ResultsIn each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo-R2 range 0.8-3.7%; minimum p = 4 × 10-23).ConclusionsThese results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder.
| S-EPMC5643224 | biostudies-literature
Project description:BackgroundA recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).MethodsThe discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8-40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.ResultsWhen combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).ConclusionsWe detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
| S-EPMC9693667 | biostudies-literature
Project description:ObjectiveComorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS.MethodsUsing a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome-wide association study and was tested using regression.ResultsA total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta-analyses identified that in MS, each 1-SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09-1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease.InterpretationHigher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.
| S-EPMC11187942 | biostudies-literature
Project description:Higher prevalence of autism in offspring born to mothers with rheumatoid arthritis has been reported in observational studies. We investigated (a) the associations between maternal and offspring's own genetic liability for rheumatoid arthritis and autism-related outcomes in the offspring using polygenic risk scores (PRS) and (b) whether the effects were causal using Mendelian randomization (MR). Using the latest genome-wide association (GWAS) summary data on rheumatoid arthritis and individual-level data from the Avon Longitudinal Study of Parents and Children, United Kingdom, we constructed PRSs for maternal and offspring genetic liability for rheumatoid arthritis (single-nucleotide polymorphism [SNP] p-value threshold 0.05). We investigated associations with autism, and autistic traits: social and communication difficulties, coherence, repetitive behaviours and sociability. We used modified Poisson regression with robust standard errors. In two-sample MR analyses, we used 40 genome-wide significant SNPs for rheumatoid arthritis and investigated the causal effects on risk for autism, in 18,381 cases and 27,969 controls of the Psychiatric Genetics Consortium and iPSYCH. Sample size ranged from 4992 to 7849 in PRS analyses. We found little evidence of associations between rheumatoid arthritis PRSs and autism-related phenotypes in the offspring (maternal PRS on autism: RR 0.89, 95%CI 0.73-1.07, p = 0.21; offspring's own PRS on autism: RR 1.11, 95%CI 0.88-1.39, p = 0.39). MR results provided little evidence for a causal effect (IVW OR 1.01, 95%CI 0.98-1.04, p = 0.56). There was little evidence for associations between genetic liability for rheumatoid arthritis on autism-related outcomes in offspring. Lifetime risk for rheumatoid arthritis has no causal effects on autism.
| S-EPMC8755835 | biostudies-literature
Project description:We studied attentional modulation of cortical processing of faces and houses with functional MRI and magnetoencephalography (MEG). MEG detected an early, transient face-selective response. Directing attention to houses in "double-exposure" pictures of superimposed faces and houses strongly suppressed the characteristic, face-selective functional MRI response in the fusiform gyrus. By contrast, attention had no effect on the M170, the early, face-selective response detected with MEG. Late (>190 ms) category-related MEG responses elicited by faces and houses, however, were strongly modulated by attention. These results indicate that hemodynamic and electrophysiological measures of face-selective cortical processing complement each other. The hemodynamic signals reflect primarily late responses that can be modulated by feedback connections. By contrast, the early, face-specific M170 that was not modulated by attention likely reflects a rapid, feed-forward phase of face-selective processing.
| S-EPMC1348001 | biostudies-literature
Project description:BackgroundUnusual behavioral reactions to sensory stimuli are frequently reported in individuals on the autism spectrum (AS). Despite the early emergence of sensory features (< age 3) and their potential impact on development and quality of life, little is known about the neural mechanisms underlying sensory reactivity in early childhood autism.MethodsHere, we used electroencephalography (EEG) to investigate tactile cortical processing in young children aged 3-6 years with autism and in neurotypical (NT) children. Scalp EEG was recorded from 33 children with autism, including those with low cognitive and/or verbal abilities, and 45 age- and sex-matched NT children during passive tactile fingertip stimulation. We compared properties of early and later somatosensory-evoked potentials (SEPs) and their adaptation with repetitive stimulation between autistic and NT children and assessed whether these neural measures are linked to "real-world" parent-reported tactile reactivity.ResultsAs expected, we found elevated tactile reactivity in children on the autism spectrum. Our findings indicated no differences in amplitude or latency of early and mid-latency somatosensory-evoked potentials (P50, N80, P100), nor adaptation between autistic and NT children. However, latency of later processing of tactile information (N140) was shorter in young children with autism compared to NT children, suggesting faster processing speed in young autistic children. Further, correlational analyses and exploratory analyses using tactile reactivity as a grouping variable found that enhanced early neural responses were associated with greater tactile reactivity in autism.LimitationsThe relatively small sample size and the inclusion of a broad range of autistic children (e.g., with low cognitive and/or verbal abilities) may have limited our power to detect subtle group differences and associations. Hence, replications are needed to verify these results.ConclusionsOur findings suggest that electrophysiological somatosensory cortex processing measures may be indices of "real-world" tactile reactivity in early childhood autism. Together, these findings advance our understanding of the neurophysiological mechanisms underlying tactile reactivity in early childhood autism and, in the clinical context, may have therapeutic implications.
| S-EPMC8017878 | biostudies-literature
Project description:Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18-31 (beta coefficients ranged from 0.02-0.06, p-values ranged from 10-6-10-12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective.
| S-EPMC6826735 | biostudies-literature
Project description:Cortical areas in the ventral visual pathway become selectively tuned towards the processing of faces compared to non-face stimuli beginning around 3 months of age and continuing over the first year. Studies using event-related potentials in the EEG (ERPs) have found an ERP component, the N290, that displays specificity for human faces. Other components, such as the P1, P400, and Nc have been studied to a lesser degree in their responsiveness to human faces. However, little is known about the systematic changes in the neural responses to faces during the first year of life, and the localization of these responses in infants' brain. We examined ERP responses to pictures of faces and objects in infants from 4.5 months through 12 months in a cross-sectional study. We investigated the activity of all the components reported to be involved in infant face processing, with particular interest to their amplitude variation and cortical localization. We identified neural regions responsible for the component through the application of cortical source localization methods. We found larger P1 and N290 responses to faces than objects, and these components were localized in the lingual and middle/posterior fusiform gyri, respectively. The amplitude of the P400 was not differentially sensitive to faces over objects. The Nc component was different for faces and objects, was influenced by the infant's attentional state, and localized in medial-anterior brain areas. The implications of these results are discussed in the identification of developmental ERP precursors to face processing.
| S-EPMC7085434 | biostudies-literature